ABSTRACT
Cutaneous squamous cell carcinoma (cSCC) is the second most common type of non-melanoma skin cancer. Platinum-based regimens have been an integral part of palliative care for patients with locally advanced or metastatic disease. There is no evidence of efficacy for later lines of chemotherapy and no targeted therapy has been introduced as 'standard of care'. Here we report on the case of an elderly cSCC patient, resistant to conventional therapy, however successfully treated with anti-epidermal growth factor receptor (EGFR) agent (Cetuximab) in addition to a daily dose of Curcumin phospholipid. The patient responded to treatment and experienced no recurrence for 11 months with only minor skin-related toxicity. To our knowledge, this is the first report of clinical evidence that an anti EGFR targeted therapy with a daily oral dose of Curcumin phospholipid is well tolerated and results in a highly effective disease control in a heavily pretreated cSCC patient.
ABSTRACT
Transforming Growth Factor-beta1 (TGF -beta1) is a multifunctional cytokine that regulates a number of cellular processes such as cell growth, differentiation, plasticity, cell motility, adhesiveness, embryogenesis, development and apoptosis through binding to TGF-beta receptors. We have previously demonstrated that K-ras-transformed rat thyroid cells, K10, are resistant to the growth inhibitory action of TGF-beta1, because they show a decreased expression of type II receptor (TbetaRII). Clones obtained transfecting TbetaRII, partially revert their malignant phenotype, showing a reduction in the anchorage-dependent and -independent cell growth and a statistically significant decrease in tumourigenicity with respect to the highly malignant parental cells, both in spontaneous and artificial metastases, when transplanted in athymic nude mice. The purpose of the present work is to elucidate the molecular events involved in the modulation of the tumourigenic potential of K-ras-transformed rat thyroid cells overexpressing TbetaRII. Our data demonstrate that the TbetaRII overexpressed in K-ras-transformed thyroid cell clones is a functional receptor and is essential to restore in these cells behaviour similar to that of control cells. The TbetaRII overexpression is responsible for a strong reduction of adhesive and migratory behaviour of highly malignant K-ras-transformed thyroid cells. These results suggest that the restore of a functional TGF-beta receptor in these cells may be useful for the limitation of tumour spread and dissemination.